Jordi Pérez-López1, Montserrat Morales-Conejo2, Mónica López-Rodríguez3, Álvaro Hermida-Ameijeiras4, Marc Moltó-Abad5. 1. Unit of Rare Diseases, Hospital Vall d'Hebron, Barcelona, Spain. Electronic address: jordpere@vhebron.net. 2. Department of Internal Medicine, Hospital 12 de Octubre, Madrid, Spain. 3. Department of Internal Medicine, Hospital Central de la Cruz Roja, Madrid, Spain. 4. Unit of Inborn Errors of Metabolism, Department of Internal Medicine, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain. 5. Unit of Rare Diseases, Hospital Vall d'Hebron, Barcelona, Spain.
Abstract
BACKGROUND: The efficacy of starting enzyme replacement therapy (ERT) in adults with Muchopolysaccharidosis Type I (MPS-I) is controversial. Evaluating the benefits reported by patients initiating ERT with laronidase at adult age might help physicians decide whether the use of ERT in these patients is worthwhile from a clinical point of view. OBJECTIVE: To assess every effectiveness variable modified in MPS-I patients who initiated laronidase at adult age. METHODS: A systematic search of the literature, from inception to July 2016, was conducted using MEDLINE, EMBASE, CENTRAL and LILACS to identify randomized trials or observational studies including ≥1 MPS-I patients with ERT initiated in adult age (≥18years) and evaluating ERT efficacy. A meta-analysis of studies evaluating the same effectiveness outcome was performed and the evidence was rated according to GRADE criteria. Heterogeneity was assessed by the Chi-squared test and the I-squared statistic. Case reports were excluded from meta-analysis but their main outcomes were separately evaluated. The decrease in urine glycosaminoglycans (uGAGs) levels as patient percentage with reduction in uGAGs and with normalization was the primary outcome. RESULTS: Nineteen clinical studies and 12 case reports were selected. ERT decreased uGAG levels (high evidence) and liver volume (high), improved 6-min walking test (6MWT) (moderate) and increased blood anti-ERT antibody levels (high). There was no conclusive results (low or very low evidence) regarding improvement/stabilization of respiratory function, change in shoulder flexion, cardiac improvement/stabilization, improvement in symptoms of nocturnal hypoventilation and sleep apnea, improvement in quality of life, visual acuity, otolaryngologic function, bone mineral density or effectiveness of intrathecal therapy. LIMITATIONS: Excluding case reports, there was no study conducted specifically in the target population (ERT ≥18years). Data were from subgroup analyses of selected studies. There was a great heterogeneity between designs and clinical outcomes evaluated. CONCLUSIONS: ERT improves uGAGs and liver volume in MPS-I patients initiating therapy as adults, although the putative clinical benefit associated to these improvements is unclear. Moderate evidence was shown for improvement in 6MWT. Systematic review registration number (PROSPERO): 42,016,041,306.
BACKGROUND: The efficacy of starting enzyme replacement therapy (ERT) in adults with Muchopolysaccharidosis Type I (MPS-I) is controversial. Evaluating the benefits reported by patients initiating ERT with laronidase at adult age might help physicians decide whether the use of ERT in these patients is worthwhile from a clinical point of view. OBJECTIVE: To assess every effectiveness variable modified in MPS-Ipatients who initiated laronidase at adult age. METHODS: A systematic search of the literature, from inception to July 2016, was conducted using MEDLINE, EMBASE, CENTRAL and LILACS to identify randomized trials or observational studies including ≥1 MPS-Ipatients with ERT initiated in adult age (≥18years) and evaluating ERT efficacy. A meta-analysis of studies evaluating the same effectiveness outcome was performed and the evidence was rated according to GRADE criteria. Heterogeneity was assessed by the Chi-squared test and the I-squared statistic. Case reports were excluded from meta-analysis but their main outcomes were separately evaluated. The decrease in urine glycosaminoglycans (uGAGs) levels as patient percentage with reduction in uGAGs and with normalization was the primary outcome. RESULTS: Nineteen clinical studies and 12 case reports were selected. ERT decreased uGAG levels (high evidence) and liver volume (high), improved 6-min walking test (6MWT) (moderate) and increased blood anti-ERT antibody levels (high). There was no conclusive results (low or very low evidence) regarding improvement/stabilization of respiratory function, change in shoulder flexion, cardiac improvement/stabilization, improvement in symptoms of nocturnal hypoventilation and sleep apnea, improvement in quality of life, visual acuity, otolaryngologic function, bone mineral density or effectiveness of intrathecal therapy. LIMITATIONS: Excluding case reports, there was no study conducted specifically in the target population (ERT ≥18years). Data were from subgroup analyses of selected studies. There was a great heterogeneity between designs and clinical outcomes evaluated. CONCLUSIONS: ERT improves uGAGs and liver volume in MPS-Ipatients initiating therapy as adults, although the putative clinical benefit associated to these improvements is unclear. Moderate evidence was shown for improvement in 6MWT. Systematic review registration number (PROSPERO): 42,016,041,306.
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